Abstract
Pharmacokinetic (PK) studies play an important role in identifying lead compounds for further development. Typically rats are used for PK screening of New Chemical Entities (NCEs) as the compound requirements are minimal (<10 mg), multiple blood sampling (up to 10 samples) can be performed from the same animal and in small volumes (5-25μL) for sample analysis. Blood sampling site is critical in obtaining multiple blood samples of good quality and in small volumes with minimal stress to animals. However, it is not known whether PK parameters can be influenced by sampling site. Thus, in this study, we evaluated the effect of different blood sampling sites like retro-orbital plexus, jugular vein and saphenous vein on PK parameters of Dapsone. Dapsone was administered both orally and intravenously at a dose of 12 mg/kg to a group of 4 male Sprague Dawley rats and blood samples were collected up to 24 h. Samples were analyzed by LC/MS/MS and PK parameters were calculated. With all the sampling techniques, PK parameters like clearance, volume of distribution, half-life and bioavailability were similar. Due to the control on the blood volume withdrawn at each time point, quick sampling with minimal hemolysis and minimal animal handling stress during sampling, Jugular Vein (JV) or Saphenous Vein (SV) sampled rats can be used for PK studies. Further for saphenous sampling no pre-study preparation like cannulation is required before dosing the animals therefore sampling of rats through saphenous vein is recommended for pharmacokinetic and toxicokinetic studies. To summarize, SV sampling reduce the number of animals in different Pharmacokinetic (PK) (mouse) and Toxicokinetic (TK) (mouse and rat) studies by using serial draws, offers reduction and refinement over the othersampling techniques with minimal preparation upfront and with a potential to replace them.
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